In practice, several thousand samples pass through state-of-the-art automated laboratory installations every day. With the help of laboratory management software, these samples are managed and sent to the appropriate test equipment according to the requested diagnostic tasks, and the test results are archived and sent out. Samples intended for later use can easily be sequestered out of this process. Thus far, however, there has been no simple possibility for suitably dividing these samples into portions (aliquoting) as quickly as possible (above all in an automated manner) and cooling them to a suitable storage temperature as soon as possible.
Aliquoting is usually carried out by means of automated pipetting devices which detect (compare to the database) the sample tubes in which the samples arrive at the laboratory and which are labeled with bar codes, take up (suction, aspirate) the samples by means of pipette tips or dispensing needles of an automated pipetting device and divide them into aliquots (fractions of the sample) by distributing them to a plurality of tube-shaped vessels which are suitable for freezing and which are likewise coded. Commonly used sampling tubes are manufactured by Sarstedt, e.g., Monovette®, and BD, e.g. Vacutainer®.
Tube-shaped vessels (crytotubes with two-dimensional bar codes) manufactured by Thermo Matrix, Thermo Scientific, ABgene or FluiX, for example, are used for the aliquots. These tube-shaped vessels are in turn usually supplied in plastic racks (tube racks) in 8×12 format (eight rows A-H and twelve columns, 1-12).
The aliquots are often 1-ml portions of the serum supernatant of the samples. However, other components of a blood sample or completely different biological samples are also possible (other body fluids or dissolved biochemical samples, also separate from any solvents that may be needed).
Four temperature ranges are considered practical to employ for the processing and storage of samples. Fast processing of liquid samples at room temperature, intermediate storage at −20° C. for the space of a few hours, storage at −80° C. for many weeks and months, and indefinite storage under actual cryogenic conditions, i.e., in liquid nitrogen at 77° K. In routine laboratory practice, this is often carried out in stages. Accordingly, insertion into the −80° C. area of an automatic storage is often carried out via a −20° C. interface system (e.g., Liconic ULT Store). A cold box according to the invention serves as −20° C. intermediate storage and is used irrespective of the further use of the sample.
In current practice, the tube-shaped vessels with the samples which often arrive in the laboratory at indeterminate times are filled at room temperature and are loaded into a rack so that the rack is completely filled before inserting it into a cooling device or the rack is placed in a cassette having a plurality of places for the racks, and the cassette which is completely filled with racks is then inserted into a cooling device, e.g., the STT3k0-DF by Liconic AG. The individual samples are exposed to room temperature for various lengths of time before being inserted into the cooling devices, which leads to a loss of quality as was mentioned above.
It is the object of the invention to find a solution by which samples arriving in a laboratory at different times and in different quantities can be cooled to a cooling temperature within a very short time.
The object of the invention is met by a cold box with a rack loaded with tube-shaped vessels for automated filling by an automated pipetting device. This cold box has a bottom part and a lid part, a rack which is loaded with tube-shaped vessels in a matrix of rows and columns, wherein the rows extend along the width of the rack and the columns extend along the length of the rack, a cooling receptacle which is enclosed by thermal insulation and which is at least partially arranged in the bottom part and which is adapted to the outer dimensions of the loaded rack, and in which the loaded rack is placed.
The lid part comprises a lid frame and a lid which is movable in the lid frame in direction of the columns or rows of the rack and in which is provided a quantity of openings which are adapted to the circumference size of a commercially available pipette tip/dispensing needle of an automated pipetting device so that one of the openings can be positioned over each individual tube-shaped vessel in the rack. The lid completely covers the cooling receptacle in every position so that a dry protective gas with which the cooling receptacle is filled and which is heavier than air remains in the cooling receptacle. The cold box further has a cooling device which is integrated in the thermal insulation in the bottom part and which contacts the cooling receptacle.
The lid is advantageously formed of an outer lid with a cutout which reaches at least over the length of a column and an inner lid which is adjustable relative to the outer lid and which covers the cutout. The at least one opening is a through-hole in the inner lid and can be positioned with respect to the tube-shaped vessels by moving the outer lid and adjusting the inner lid.
It is advantageous when the cooling receptacle is located partly in the bottom part and partly in the lid part, and the portion of the cooling receptacle in the lid part is formed by a formation in the thermal insulation and the portion of the cooling receptacle in the bottom part is formed by a trough. The rack advantageously sits on a tray with two tray handles for easy insertion and removal of the rack. Two opposing recesses are provided in the formation of the thermal insulation for the tray handles, and the tray handles are received in these recesses.
To fill the cooling receptacle, it is advantageous to provide a feed line for the protective gas in the bottom part. The cooling device advantageously comprises a plate-shaped Peltier cooler and a liquid circulating cooler. The Peltier cooler communicates directly with the trough on the one hand and with the liquid circulating cooler on the other hand. In order for the lid to completely cover the cooling receptacle in every position, this lid is movable proceeding from a central position in positive or negative direction by one half of the length of the rack between two end positions and the length of the lid is selected correspondingly. The inner lid is advantageously integrated in the outer lid. The outer lid and the inner lid can also be arranged one above the other so as to overlap.
In a preferred embodiment form of the cold box, the inner lid is round and is rotatable by at least 180° around the geometric center of the outer lid, and the quantity of through-holes is equivalent to one half of the quantity of tube-shaped vessels arranged in a row, the through-holes being arranged on a straight line radial to the center of the outer lid. In order to be able to monitor the fill level, it is advantageous to provide a gas sensor in the cooling receptacle.